Polymeric compositions are widely used in medical applications. For example, various polymers have been used as suture materials and for fracture fixation (see e.g., U.S. Pat. Nos. 5,902,599 and 5,837,752). Polymers have also been used in polymer-based drug delivery systems. For drug delivery, polymers are typically used as a matrix for the controlled or sustained release of biologically active agents. Examples of such polymer-based drug delivery systems are described in, for example, U.S. Pat. Nos. 6,183,781, 6,110,503, 5,989,463, 5,916,598, 5,817,343, and 5,650,173. Polymers have also been used as scaffolds for tissue engineering (see e.g., U.S. Pat. No. 6,103,255). Additionally, polymers have been used in dental applications as adhesives and fillers (see e.g., U.S. Pat. No. 5,902,599).
One type of polymeric composition that has received considerable attention for medical applications is the hydrogel. Hydrogels are three-dimensional polymer networks composed of homopolymers or copolymers that are capable of absorbing large amounts of water. Thus, a characteristic of hydrogels is that they swell in water or aqueous fluids without dissolving. High water content and soft consistency make hydrogels similar to natural living tissue more than any other class of synthetic biomaterials. Accordingly, many hydrogels are compatible with living systems and hydrogels have found numerous applications in medical and pharmaceutical industries. For example, hydrogels have been investigated widely as drug carriers due to their adjustable swelling capacities, which permit flexible control of drug release rates.
Under certain situations, it may be desirable to prepare a polymeric composition such as a hydrogel at the site of its intended use. However, a disadvantage of some polymeric compositions is that the polymers must be formed before they can be used. This is because the preparation of many types of polymers typically requires extreme conditions that are not compatible with the environment that the polymeric composition is intended to be used in (e.g., uses in biological systems). For example, the preparation of some polymers can require high temperature, exotic reagents, initiators, and/or solvents, and expensive and/or toxic catalysts. Another reason for preparing a polymeric composition before it can be used is that polymers are typically prepared from reactive monomers or oligomers, which, instead of forming the desired polymer network, can react with cells, tissues, biomolecules, and other species present in a given application.
Similar problems also exist when using polymeric compositions that require crosslinking, which is the formation of a linkage (e.g., covalent, non-covalent, or combinations thereof) between polymer chains or between portions of the same polymer chain. Crosslinking is frequently accomplished through the introduction of a crosslinker that has functionality capable of reacting chemically with functionality on one or more polymer chains. Crosslinking is often done to provide rigidity to the polymer system. For hydrogels, the polymer network is created by forming crosslinks between polymeric chains. For many polymeric compositions, extreme conditions and reactive crosslinkers are required for crosslinking. And as discussed above, such conditions are not generally compatible with certain environments (e.g., biological systems). Thus, crosslinking is often performed prior to using a polymer composition in a given application.
It can be desirable in certain applications to have crosslinking that is reversible, e.g., one or more crosslinks can be formed, broken, and reformed in the same or different location in the polymer network. Gels that dynamically restructure are commonly observed in nature, including synovial fluid (Balazs and Gibbs, Chem Mol Biol Intercell Matrix, Advan Study Inst 3:1241-53, 1970; Gibbs et al., Biopolymers 6:777-91, 1968) and mucins (Pearson et al., Methods in Molecular Biology, 125:99-109, 2000). Such materials are the subject of intense investigation for fundamental material science and advanced biomaterial applications, such as artificial biofluids and biosolids, cell encapsulation, tissue engineering and injectable drug delivery. The balance of solid-like and fluid-like behavior within such a gel typically results from the chemical equilibrium of reversible crosslinking interactions between polymer chains (Franse, Polymer Materials and Engineering 142, 2002; Goodwin et al., Rheology for Chemists: An Introduction, 2000). Contemporary research on viscoelastic gels focuses on exploiting hydrogen bonding interactions in protein-based networks or other self-assembled systems (Aggeli et al., Nature 386:259-62, 1997; Nowak et al., Nature 417:424-28, 2002; Sijbesma et al., Science 278:1601-04, 1997; Wang et al., Nature 397:417-20, 1999; Lin et al., J Biomech Eng 126:104-10, 2004; Petka et al., Science 281:389-92, 1998). Reversible covalent crosslinks (Boeseken, Adv Carbohydrate Chem 4:189-210, 1949; Lorand and Edwards, J Org Chem 24:769-74, 1959; Sugihara and Bowman, J Am Chem Soc 80:2443-46, 1958), on the other hand, could provide an energetically favorable, specific and controlled mechanism for engineering the viscoelasticity of gel networks (Bucci et al., Polymer Preprints 32:457-8, 1991; Pezron et al., Macromolecules 21:1121-5, 1988; Schultz and Myers, Macromolecules 2:281-85, 1969).
The wide variety of medical applications for polymeric compositions demonstrates the need for the development of different types of compositions with varying physical properties for use in various applications (e.g., medical applications). Further it would be desirable in some instances to have polymeric compositions that can be prepared or crosslinked in situ in a biological environment under mild conditions. Still further, it would be desirable in some instances to have polymeric compositions that can change their viscoelastic properties under certain conditions. The subject matter disclosed herein meets these and other needs.